The effect of various protease inhibitors on the course of development of experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN) will be investigated. Lewis rats will be injected with purified CNS (or PNS) myelin incorporated into Freund's adjuvant. Daily injection of various protease inhibitors including leupeptin, antipain, epsilon-amino caproic acid, pepstatin, trasylol, trans-4-aminomethylcyclohexane-1-carboxylic acid, p-nitrophenylguanidinobenzoate, and polylysine will begin on day 7 and continue one or two times daily throughout the course of the disease. At specified intervals, day 10, day 14, and day 21 after myelin injection various organs will be removed and assayed for levels of neutral and acid proteinase using myelin basic protein as a substrate. Spinal cord samples from each animal will be fixed and examined histologically for lesions of EAE. Spinal roots will be examined for lesions in animals injected with PNSmyelin. Assessment of the efficacy of the inhibitors will be made on the basis of clinical signs of disease, time of onset of disease, degree of weight loss, and severity of histological lesions. An attempt will be made to correlate the degree of protection from the autoimmune disease with inhibition of proteolytic activity in CNS (or PNS) and in various tissues.